TSPO配体化合物YL-IPA08抗抑郁作用及其可能机制的研究

Antidepressant-like effect of YL-IPA08,a TSPO ligand,and its possible mechanism

目的探讨TSPO配体化合物YL-IPA08的抗抑郁作用及其机制。方法与结果在小鼠悬尾模型和大鼠强迫性游泳模型上,单次给予YL-IPA08分别显著缩短悬尾和游泳不动时间,有效剂量分别为0.1-0.3 mg/kg（po）和1-10 mg/kg（po）;分别与阳性对照药度洛西汀（DLX,10 mg/kg,po）和地昔帕明（DMI,30 mg/kg,po）作用一致。在小鼠悬尾模型上,单独给予TSPO特异性拮抗剂PK11195（3 mg/kg,ip）对悬尾不动时间无明显影响,但可以显著阻断YL-IPA08（0.1 mg/kg）在该模型上的抗抑郁效应。以ELISA或放免法检测发现,急性给予YL-IPA08（3,10mg/kg,po）使强迫性游泳后大鼠血清孕烯醇酮或孕酮含量显著增加。结论 YL-IPA08在动物模型上具有抗抑郁作用,该作用可能与激活TSPO,促进神经类固醇生物合成有关。

Objective To investigate the antidepressant-like effect of YL-IPA08（a new TSPO ligand） and the possible mechanism.Methods and Results In the tail-suspension test in mice and the forced swimming test in rats,the administration of YL-IPA08 significantly reduced the immobility time.The effective doses were 0.1-0.3 mg/kg（po） and 1-10 mg/kg（po）,respectively.These effects of YL-IPA08 were similar to those of duloxetine（10 mg/kg,po） and desipramine（30 mg/kg,po）.The administration of PK11195（3 mg/kg,ip）,a selective antagonist of TSPO,did not interfere with the immobility time in the tail-suspension test in mice.Nevertheless,PK11195 coadministration blocked the antidepressant-like effect of YL-IPA08（0.1 mg/kg,po） in this model.Moreover,an acute administration of YL-IPA08（3 and 10 mg/kg,po）was found to increase the levels of pregnenolone or progesterone in the rat serum after the forced swimming test by ELISA or radioimmunoassay.Conclusion YL-IPA08 has the antidepressant effect in animal behavior models,which may be related to the activation of TSPO and the promotion of neurosteroid biosynthesis.